The human malaria parasite, Plasmodium falciparum, has a complex life cycle. The parasite undergoes not only various stage transformations but also different host cell environments. It is essential for the adapting parasite to develop mechanisms, such as protein secretion and translocation, to survive and prevail. Rab proteins - We decided to examine whether Rab proteins, the major molecular components of the secretory machinery and conserved amongst eukaryotes, may play a role in Plasmodium protein secretion and translocation. Rab proteins are a group of 20-30 kDa Ras-like GTP-binding proteins involved in regulation of cell proliferation and differentiation. We have identified, to date, three different Rab genes from the cDNA library. Their expression in the parasite is developmentally regulated. Overall homology of these Rab proteins to one another is close to 50%. Stress Proteins - The heat shock proteins have been identified to be involved in the major cellular machinery for protein secretion and translocation, and are essential for cellular survival. We have cloned and sequenced the cDNA encoding two major heat shock proteins, hsp90 and hsp60. Both Plasmodium heat shock proteins exhibit strong homology with other eukaryotic analogs (hsp60, 50%; hsp90, 60%). In the merozoite and gamete stages, the constitutive level of hsp60 expression remains very low while that of hsp90 is compatible to hsp70. The induction of both proteins follows the characteristics of a true heat shock protein with rapid elevation after a rise in temperature.